Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A.

Pub Date : 2023-12-01 Epub Date: 2023-05-25 DOI:10.1080/01478885.2023.2215151
Jie Tan, Mingtao Chen, Meng Liu, Aifang Chen, Min Huang, Xiaoli Chen, Xia Tian, Wei Chen
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Abstract

Bone marrow mesenchymal stem cell (BSMC)-derived extracellular vehicles (EVs) have a pivotal therapeutic potential in hepatic fibrosis (HF). Activation of hepatic stellate cells (HSCs) is the key mechanism in HF progression. Downregulation of miR-192-5p was previously observed in activated HSCs. Nonetheless, the functions of BSMC-derived exosomal miR-192-5p in activated HSCs remain unclear. In this study, transforming growth factor (TGF)-β1 was used to activate HSC-T6 cells to mimic HF in vitro. Characterization of BMSCs and BMSC-derived EVs was performed. Cell-counting kit-8 assay, flow cytometry, and western blotting revealed that TGF-β1 increased cell viability, promoted cell cycle progression, and induced upregulation of fibrosis markers in HSC-T6 cells. Overexpression of miR-192-5p or BMSC-derived exosomal miR-192-5p suppressed TGF-β1-triggered HSC-T6 cell activation. RT-qPCR revealed that protein phosphatase 2 regulatory subunit B'' alpha (PPP2R3A) was downregulated in miR-192-5p-overexpressed HSC-T6 cells. Luciferase reporter assay was used for verifying the relation between miR-192-5p and PPP2R3A, which showed that miR-192-5p targeted PPP2R3A in activated HSC-T6 cells. Collectively, BMSC-derived exosomal miR-192-5p targets PPP2R3A and inhibits activation of HSC-T6 cells.

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骨髓间充质干细胞分泌的外泌体miR-192-5p抑制肝星状细胞活化并靶向PPP2R3A。
骨髓间充质干细胞(BSMC)衍生的细胞外载体(ev)在肝纤维化(HF)中具有关键的治疗潜力。肝星状细胞(HSCs)的活化是HF进展的关键机制。先前在活化的hsc中观察到miR-192-5p的下调。尽管如此,bsmc来源的外泌体miR-192-5p在活化的hsc中的功能尚不清楚。本研究采用转化生长因子(TGF)-β1激活HSC-T6细胞体外模拟HF。对骨髓间充质干细胞和骨髓间充质干细胞衍生的电动汽车进行表征。细胞计数试剂盒-8、流式细胞术、western blotting检测结果显示,TGF-β1可提高HSC-T6细胞活力,促进细胞周期进程,诱导纤维化标志物上调。过表达miR-192-5p或bmsc来源的外泌体miR-192-5p可抑制TGF-β1触发的HSC-T6细胞活化。RT-qPCR结果显示,在mir -192-5p过表达的HSC-T6细胞中,蛋白磷酸酶2调控亚基B α (PPP2R3A)下调。采用荧光素酶报告基因法验证miR-192-5p与PPP2R3A的关系,结果表明,在活化的HSC-T6细胞中,miR-192-5p靶向PPP2R3A。总的来说,bmsc来源的外泌体miR-192-5p靶向PPP2R3A并抑制HSC-T6细胞的活化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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